1. Field of the Invention
This invention relates to NMR shift reagents and in particular contrast enhancing agents for magnetic resonance imaging.
2. Prior Art
Magnetic Resonance (hereinafter MR) imaging is one of the newest methods of viewing the interior of the human body. Radio waves interact with protons in a magnetic field to produce images having superior contrast compared to X-ray tomography. However, the technique can be non-specific, that is, it may be impossible to distinguish from between many pathological conditions, such as between cancer and the edema surrounding the cancer.
Contrast agents enhance various portions of the MR image by changing, usually decreasing, the relaxation times of the protons in the immediate vicinity to the agent. One example of a contrast agent is that disclosed in the European Patent 3,302,410 of A. G. Schering for gadolinium diethyline triamine pentaacetic acid complex (hereinafter Gd DTPA). Gd DTPA has been attached to a variety of macromolecules, for example monoclonal antibodies, albumin, and dihexadecylamine.
Other agents, such as ethylene diamine tetraacetic acid (hereinafter EDTA), and 1, 4, 7, 10 tetraacetic acid (hereinafter DOTA), have been chelated with Gd in an effort to make a superior contrast agent.
Prior art chelates of Gd, and other paramagnetic metals, suffer from several defects. The body rapidly excretes Gd DTPA, for example. It is not organ specific and stays within the extra-cellular space. As a result, the only organs suitably enhanced with Gd DTPA are kidneys and areas of abnormal brain permeability. Since magnetic resonance imaging requires long data acquisition times rapidly metabolized enhancing agents do not work well.
Another problem with known MR enhancing agents is that the proteins that are used to anchor the simple chelates, monoclonal antibodies and the like, may provoke allergic reactions in the recipient.
It would therefore be advantageous to have a MR contrast enhancing agent that was metabolized slowly in vivo, was organ specific, and did not provoke allergic reactions in the recipient.